Promoter activity and gene structure of rabbit FKBP52

Abstract

A 0.9-kb fragment situated directly upstream of the first ATG of rabbit FKBP52 is rich in acceptor sites for transcription factors, contains a CAAT box at -197 and could represent the proximal promoter of this immunophilin. Transvection analysis of this fragment showed strong promoter activity on the expression of a reporter gene. Deletions at the 5' end of this fragment showed that a basic sequence of 155 base pairs upstream of the CAAT box was sufficient to enhance luciferase expression an average 220-fold compared to the empty vector. This sequence, which contains acceptor sites for transcription factors of the EGR family and heat-shock factors, is closely homologous to 110 base pairs situated directly 5' of FKBP52 exon 1 in human chromosome 12p13.3, suggesting that these transcription factors could be involved in the regulation of the gene in both species. Furthermore, the upstream region of RbFKBP52 contains a large proportion of SINEs (C-repeats, Alu analogs), some of which include the A and B boxes required for transcription of RNA polymerase III, and poly A tracts. RbFKBP52, like HuFKBP52, is made up of 10 exons and 9 introns, a feature shared with other large immunophilins such as FKBP65 and Cyclophilin 40, and which appears widely conserved.